Summary of Work: The cognitive deficits produced by infection with HIV-1 are reported to be the leading cause of dementia among humans under 40 worldwide. HIV kills neurons indirectly by infecting monocytic cells in the CNS called microglia which release neurotoxic cytokines. The HIV coat protein, gp120, promotes microglial infection by binding to a G protein coupled receptor, CXCR4, which is normally activated by the chemokine SDF-1. We have recently identified Rho family GTPases as the effectors for hormonal regulation of potassium channels. We have also implicated potassium channels in the regulation of lymphocyte migration and cell fate. Therefore, we are investigating the mechanism of potassium channel regulation by SDF-1 in microglia, and the effects of gp120 on this process. The goal is identifying new therapeutic targets for controlling microglial activation and subsequent neuronal injury.